Studies of aging in Ames dwarf mice: Effects of caloric restriction

Ames dwarf mice, which are small and deficient in growth homone (GH), prola ctin (PRL), and thyroid stimulating hormone (TSH) live much longer (1-1.25 years) than their normal siblings. It was of interest to examine the respon se of these animals to caloric restriction (CR) because of the possibility that dwarf mice are voluntarily caloric restricted. We are testing the hypo thesis that this possible natural caloric restriction will negate any benef its of an imposed CR on lifespan. Male and female Ames dwarf mice and their normal counterparts have been fed ad libitum (AL) or a 30% CR diet for 25-29 months. Animals were monitored daily and weighed weekly. At 12-15 months of age, CR mice weighed significa ntly less than their AL fed counterparts (normal females: -42%, normal male s: -23%, dwarf females: -18.8%, and dwarf males: -22.2%). Only in dwarf fem ales has this significant difference disappeared with age. At one year of a ge, a comparison of daily food consumption revealed that female dwarf mice consume significantly more food per gram body weight than normal females an d a similar tendency is evident for males. Although they received 30% less food, CR mice ate the same amount as AL mice per gram body weight. On measures of total locomotor activity, CR mice were significantly more ac tive than their AL-fed counterparts. On an inhibitory avoidance learning ta sk, 18-21 month old dwarf mice exhibited significantly better retention tha n their age- and diet-matched normal counterparts. Histopathological analys is in aging dwarf versus normal mice suggested that the incidence of tumors does not differ between the two groups but tumors appear to develop later in dwarf than in normal mice. After 2.25 years on the study 27% of AL normals, 52% of CR normals, 74% of AL dwarfs, and 87% of CR dwarfs are still alive. We conclude that Ames dwar fs are not CR mimetics although they share many characteristics. It remains to be determined whether CR will delay aging and cause a further life exte nsion in Ames dwarf mice.